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Clin Infect Dis. 2019 May 25. pii: ciz443. doi: 10.1093/cid/ciz443. [Epub ahead of print]

Depot medroxyprogesterone acetate and the vaginal microbiome as modifiers of tenofovir diphosphate and lamivudine triphosphate concentrations in the female genital tract of Ugandan women: Implications for TDF/3TC in pre-exposure prophylaxis.

Author information

1
Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
2
Makerere University-John Hopkins University Research Collaboration, Kampala, Uganda.
3
Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
4
School of Clinical Sciences, University of the Witwatersrand, Durban, South Africa.
5
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
6
Department of Pathology, John Hopkins University, Baltimore, Maryland, USA.
7
Department of Medicine, John Hopkins University, Baltimore, Maryland, USA.
8
College of Health Sciences, Makerere University, Kampala, Uganda.

Abstract

BACKGROUND:

Effective concentrations of antiretrovirals in the female genital tract (FGT) are critical for suppression of viral shedding or effective pre-exposure prophylaxis. The disposition of tenofovir diphosphate (TFVdp) and emtricitabine triphosphate (FTCtp) in the FGT have been previously described. Despite widespread use, however, lamivudine triphosphate (3TCtp) exposure in FGT is unknown. Depot medroxyprogesterone acetate (DMPA) and vaginal dysbiosis have been implicated in increased risk of HIV acquisition but whether they alter TFVdp or 3TCtp exposure, and therefore compromise prevention efficacy, is unknown.

METHODS:

Fifty pre-menopausal women living with HIV in Kampala, Uganda and receiving daily tenofovir disoproxil fumarate/lamivudine, were recruited. Ectocervical biopsies were obtained for quantification of TFVdp and 3TCtp using liquid chromatography-mass spectrometry. 16S rRNA gene sequencing was performed on DNA extracted from vaginal swabs. Wilcoxon rank sum was used to test for differences between contraceptive groups.

RESULTS:

3TCtp concentrations were on average 17-fold greater than TFVdp concentrations in cervical tissues. TFVdp concentrations in cervical biopsies were 76% greater in DMPA users compared to women using non-hormonal contraception (n=23/group). Abundance of Lactobacillus in vaginal swabs was correlated with 3TCtp concentrations in cervical tissues.

DISCUSSION:

We found that TFVdp concentrations were significantly greater in DMPA-users compared to women using non-hormonal contraception, suggesting prevention efficacy is unlikely to be compromised by DMPA use. Similar to reports of FTCtp, 3TCtp exposure was significantly greater than TFVdp in cervical tissue and was correlated with abundance of Lactobacillus. These data support lamivudine as an option for pre-exposure prophyalxis.

KEYWORDS:

DMPA; HIV; PrEP; lamivudine; microbiome; tenofovir

PMID:
31131846
DOI:
10.1093/cid/ciz443

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